Skip to main content
Journal of Psychiatry & Neuroscience : JPN logoLink to Journal of Psychiatry & Neuroscience : JPN
. 2000 Jan;25(1):43–47.

Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).

X M Li 1, J Chlan-Fourney 1, A V Juorio 1, V L Bennett 1, S Shrikhande 1, R C Bowen 1
PMCID: PMC1407692  PMID: 10721683

Abstract

OBJECTIVE: To investigate the effect of amitriptyline, bupropion, doxepin or venlafaxine on the gene expression of the neuroprotective enzyme superoxide dismutase (SOD1) in a catecholamine cell in vitro model. DESIGN: Molecular study of a cultured cell line. INTERVENTIONS: Rat pheochromocytoma (PC12) cells were incubated in 1 and 10 mumol/L of various antidepressant medications for 24 or 48 hours. OUTCOME MEASURES: Northern blot analysis. RESULTS: Amitriptyline up-regulated SOD1 messenger RNA in a time- and dose-dependent manner. The greatest up-regulation was following incubation with 10 mumol/L amitriptyline for 48 hours. The addition of bupropion, doxepin or venlafaxine to PC12 cell cultures also up-regulated SOD1 mRNA. CONCLUSIONS: These findings suggest that some antidepressants have the ability to positively regulate neuroprotective genes.

Full text

PDF
43

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barden N., Reul J. M., Holsboer F. Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci. 1995 Jan;18(1):6–11. doi: 10.1016/0166-2236(95)93942-q. [DOI] [PubMed] [Google Scholar]
  2. Carroll B. J., Feinberg M., Greden J. F., Tarika J., Albala A. A., Haskett R. F., James N. M., Kronfol Z., Lohr N., Steiner M. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry. 1981 Jan;38(1):15–22. doi: 10.1001/archpsyc.1981.01780260017001. [DOI] [PubMed] [Google Scholar]
  3. Cvijić G., Radojicić R., Djordjević J., Davidović V. The effect of glucocorticoids on the activity of monoamine oxidase, copper-zinc superoxide dismutase and catalase in the rat hypothalamus. Funct Neurol. 1995 Jul-Oct;10(4-5):175–181. [PubMed] [Google Scholar]
  4. Duman R. S., Heninger G. R., Nestler E. J. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997 Jul;54(7):597–606. doi: 10.1001/archpsyc.1997.01830190015002. [DOI] [PubMed] [Google Scholar]
  5. Duman R. S., Heninger G. R., Nestler E. J. Molecular psychiatry. Adaptations of receptor-coupled signal transduction pathways underlying stress- and drug-induced neural plasticity. J Nerv Ment Dis. 1994 Dec;182(12):692–700. doi: 10.1097/00005053-199412000-00003. [DOI] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Furukawa K., Estus S., Fu W., Mark R. J., Mattson M. P. Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways. J Cell Biol. 1997 Mar 10;136(5):1137–1149. doi: 10.1083/jcb.136.5.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Greenlund L. J., Deckwerth T. L., Johnson E. M., Jr Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal death. Neuron. 1995 Feb;14(2):303–315. doi: 10.1016/0896-6273(95)90287-2. [DOI] [PubMed] [Google Scholar]
  9. Hyman S. E., Nestler E. J. Initiation and adaptation: a paradigm for understanding psychotropic drug action. Am J Psychiatry. 1996 Feb;153(2):151–162. doi: 10.1176/ajp.153.2.151. [DOI] [PubMed] [Google Scholar]
  10. Jeste D. V., Lohr J. B., Goodwin F. K. Neuroanatomical studies of major affective disorders. A review and suggestions for further research. Br J Psychiatry. 1988 Oct;153:444–459. doi: 10.1192/bjp.153.4.444. [DOI] [PubMed] [Google Scholar]
  11. Knoll J. Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand Suppl. 1983;95:57–80. doi: 10.1111/j.1600-0404.1983.tb01517.x. [DOI] [PubMed] [Google Scholar]
  12. Li X. M., Chlan-Fourney J., Juorio A. V., Bennett V. L., Shrikhande S., Keegan D. L., Qi J., Boulton A. A. Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor. J Neurosci Res. 1999 Apr 1;56(1):72–75. doi: 10.1002/(SICI)1097-4547(19990401)56:1<72::AID-JNR9>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  13. Li X. M., Juorio A. V., Qi J., Boulton A. A. L-deprenyl potentiates NGF-induced changes in superoxide dismutase mRNA in PC12 cells. J Neurosci Res. 1998 Jul 15;53(2):235–238. doi: 10.1002/(SICI)1097-4547(19980715)53:2<235::AID-JNR12>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  14. Lindefors N., Brodin E., Metsis M. Spatiotemporal selective effects on brain-derived neurotrophic factor and trkB messenger RNA in rat hippocampus by electroconvulsive shock. Neuroscience. 1995 Apr;65(3):661–670. doi: 10.1016/0306-4522(94)00550-o. [DOI] [PubMed] [Google Scholar]
  15. Magariños A. M., McEwen B. S., Flügge G., Fuchs E. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci. 1996 May 15;16(10):3534–3540. doi: 10.1523/JNEUROSCI.16-10-03534.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McEwen B. S., Magarinos A. M. Stress effects on morphology and function of the hippocampus. Ann N Y Acad Sci. 1997 Jun 21;821:271–284. doi: 10.1111/j.1749-6632.1997.tb48286.x. [DOI] [PubMed] [Google Scholar]
  17. Nibuya M., Morinobu S., Duman R. S. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995 Nov;15(11):7539–7547. doi: 10.1523/JNEUROSCI.15-11-07539.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nibuya M., Nestler E. J., Duman R. S. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci. 1996 Apr 1;16(7):2365–2372. doi: 10.1523/JNEUROSCI.16-07-02365.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Plotsky P. M., Owens M. J., Nemeroff C. B. Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am. 1998 Jun;21(2):293–307. doi: 10.1016/s0193-953x(05)70006-x. [DOI] [PubMed] [Google Scholar]
  20. Rothstein J. D., Bristol L. A., Hosler B., Brown R. H., Jr, Kuncl R. W. Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4155–4159. doi: 10.1073/pnas.91.10.4155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sapolsky R. M., Krey L. C., McEwen B. S. Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci. 1985 May;5(5):1222–1227. doi: 10.1523/JNEUROSCI.05-05-01222.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sapolsky R. M., Uno H., Rebert C. S., Finch C. E. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci. 1990 Sep;10(9):2897–2902. doi: 10.1523/JNEUROSCI.10-09-02897.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwaninger M., Schöfl C., Blume R., Rössig L., Knepel W. Inhibition by antidepressant drugs of cyclic AMP response element-binding protein/cyclic AMP response element-directed gene transcription. Mol Pharmacol. 1995 Jun;47(6):1112–1118. [PubMed] [Google Scholar]
  24. Schwartzman R. A., Cidlowski J. A. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev. 1993 Apr;14(2):133–151. doi: 10.1210/edrv-14-2-133. [DOI] [PubMed] [Google Scholar]
  25. Sheline Y. I., Wang P. W., Gado M. H., Csernansky J. G., Vannier M. W. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3908–3913. doi: 10.1073/pnas.93.9.3908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stahl S. M. Basic psychopharmacology of antidepressants, part 1: Antidepressants have seven distinct mechanisms of action. J Clin Psychiatry. 1998;59 (Suppl 4):5–14. [PubMed] [Google Scholar]
  27. Stefanis L., Burke R. E., Greene L. A. Apoptosis in neurodegenerative disorders. Curr Opin Neurol. 1997 Aug;10(4):299–305. doi: 10.1097/00019052-199708000-00004. [DOI] [PubMed] [Google Scholar]
  28. Tatton W. G., Wadia J. S., Ju W. Y., Chalmers-Redman R. M., Tatton N. A. (-)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Transm Suppl. 1996;48:45–59. doi: 10.1007/978-3-7091-7494-4_5. [DOI] [PubMed] [Google Scholar]
  29. Troy C. M., Shelanski M. L. Down-regulation of copper/zinc superoxide dismutase causes apoptotic death in PC12 neuronal cells. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6384–6387. doi: 10.1073/pnas.91.14.6384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Uno H., Tarara R., Else J. G., Suleman M. A., Sapolsky R. M. Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci. 1989 May;9(5):1705–1711. doi: 10.1523/JNEUROSCI.09-05-01705.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Watanabe Y., Gould E., McEwen B. S. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res. 1992 Aug 21;588(2):341–345. doi: 10.1016/0006-8993(92)91597-8. [DOI] [PubMed] [Google Scholar]
  32. Wengenack T. M., Curran G. L., Poduslo J. F. Postischemic, systemic administration of polyamine-modified superoxide dismutase reduces hippocampal CA1 neurodegeneration in rat global cerebral ischemia. Brain Res. 1997 Apr 18;754(1-2):46–54. doi: 10.1016/s0006-8993(97)00041-3. [DOI] [PubMed] [Google Scholar]
  33. Woolley C. S., Gould E., McEwen B. S. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res. 1990 Oct 29;531(1-2):225–231. doi: 10.1016/0006-8993(90)90778-a. [DOI] [PubMed] [Google Scholar]
  34. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Psychiatry and Neuroscience are provided here courtesy of Canadian Medical Association

RESOURCES